This application seeks to investigate synaptic transmission and neuromodulation in the vertebrate retina. The focus will be at the bipolar to ganglion cell synapse. Bipolar cells have been shown in some retinas to be glutamatergic. Specifically the role of the NMDA receptor on ganglion cell activity will be investigated. In recent years the NMDA receptor has been shown to be a complex neurotransmitter receptor subtype which is modulated by extracellular glycine concentration and magnesium in relation to membrane voltage. Experiments will be carried out in the retinal slice preparation of the tiger salamander. A limited number of experiments will also be done using isolated salamander retinal cells. Whole-cell patch clamp techniques will be used to determine if the NMDA receptor on ganglion cells is modulated by extracellular substances such as magnesium or by changes in membrane voltage. The ability of NMDA to modulate action potential generation as well as synaptic input will be investigated. The role of glycine in modulating the ganglion cell NMDA receptor will be studied in addition to the regulation of glycine levels in the retina. Non-NMDA receptors elicit a transient current response due to desensitization of the receptor. The role of this transient response in shaping ganglion cell responses will be studied.